Decreased Serum Parathyroid Hormone Levels Research Articles

Differential diagnosis of hypercalcemia in a patient with CKD G5D

Patients with chronic kidney disease are characterized by the development of mineral disorders due to a decrease in the number of functioning nephrons. These changes manifest by the development of secondary hyperparathyroidism (the overproduction of intact parathyroid hormone (PTH) associated with the serum hypocalcemia, hyperphosphatemia), dysfunctional vitamin D metabolism, bone mineralization and also extraosseous calcifications. Decreased serum PTH levels associated with hypercalcemia are suspicious for adynamic bone disease, but at the same time requires an extended differential diagnostic search (e.g. metastatic processes). One of the rare causes of hypercalcemia is a defect in 24-hydroxylase (CYP24A1). We present a case of a patient on hemodialysis with atypical secondary hyperparathyroidism and an established CYP24A1 defect.

EFFICACY OF DOUBLE DOSE VERSUS STANDARD DOSE ERGOCALCIFEROL ON VITAMIN D STATUS AMONG PATIENTS WITH CHRONIC KIDNEY DISEASE

Background: Patients with chronic kidney disease (CKD) have an exceptionally high rate of 25-hydroxyvitamin D (25-OHD) deficiency. Modest supplementation with ergocalciferol to raise serum 25-OH-D levels might improve bone and mineral disorders in CKD. Limited evidence is available regarding dosage of ergocalciferol supplement in CKD populations.
 Objectives: The study aimed to examine the effectiveness of double-dose ergocalciferol on serum 25-OHD, serum intact parathyroid hormone (PTH) levels and mineral and safety profiles compared with standard-dose ergocalciferol among CKD subjects.
 Methods: The study employed a 12-week open labeled, randomized, controlled design among patients with CKD at stages III-IV and serum 25-OHD <30 ng/mL. Patients were randomized in 2 groups: standard dose treated with ergocalciferol as recommended by K/DOQI guidelines or double dose of ergocalciferol from recommendations. Serum testing including 25-OHD, intact PTH, phosphate and calcium was performed at baseline and week 12.
 Results: Sixty-three patients were included [standard-dose group (N=30) and double-dose group (N=34)]. At the end of the 12 weeks, 20 (58.8%) patients in the double dose ergocalciferol group achieved sufficiency compared with 6 (20%) patients in the standard dose ergocalciferol group (p<0.05). A significant increase in serum 25-OHD levels (13.6±9.9 vs. 8.5±6.8 ng/mL, p=0.030) and decrease in serum PTH level group (-16.8±26.4 vs. -0.3±26.8 pg/mL, p=0.030) was found in the double-dose group compared with the standard-dose group. No adverse effect was associated with the treatment.
 Conclusion: The study demonstrated that high dose oral ergocalciferol had higher efficacy to increase serum 25-OHD and decrease serum PTH levels among patients with CKD than standard-dose ergocalciferol after 12 weeks of treatment.

Effect of ferric citrate hydrate on FGF23 and PTH levels in patients with non-dialysis-dependent chronic kidney disease with normophosphatemia and iron deficiency.

In patients with normophosphatemia with chronic kidney disease (CKD), fibroblast growth factor 23 (FGF23) and parathyroid hormone (PTH) increase urinary phosphate excretion while maintaining serum phosphate within the normal range. Recent reports have shown that, in this stage, phosphate binders do not decrease serum FGF23 and PTH levels. Iron deficiency promotes transcription of FGF23 and iron-supplementation for iron deficiency decreases serum FGF23 levels. We hypothesized that ferric citrate hydrate, an iron-based phosphate binder, will decrease serum FGF23 levels in patients with non-dialysis-dependent CKD with normophosphatemia and iron deficiency. This was a single-center, randomized, open-label interventional study. The inclusion criteria were as follows: (1) eGFR<45mL/min/1.73m2, (2) normophosphatemia, (3) iron deficiency. Patients were assigned to the following groups: ferric citrate hydrate (FCH)-group, sodium ferrous citrate (SFC)-group, and control-group. After 12 weeks of intervention, we evaluated serum FGF23 levels and CKD-mineral bone disorder markers. There were 17 patients in the FCH-group, 14 in the SFC-group, and 9 in the control-group. The serum ferritin levels increased in the FCH-group and SFC-group compared with baseline. Serum FGF23 levels were unchanged; the change in the FCH-group was from 52.91RU/mL (42.48-72.91) to 40.00RU/mL (30.30-58.13) (P=0.1764). However, in the FCH-group, serum PTH levels significantly decreased compared with baseline, from 68.00pg/mL (49.00-141.00) to 60.00pg/mL (44.00-144.00) (P=0.0101). Iron-based phosphate binder did not decrease serum FGF23 levels, but decreased serum PTH levels.

Efficacy of low-dose cinacalcet on alternate days for the treatment of secondary hyperparathyroidism in hemodialysis patients: a single-center study.

IntroductionCinacalcet is effective in reducing serum parathyroid hormone (PTH) in patients with secondary hyperparathyroidism (HPT). This study focused on testing whether a prescription of low-dose cinacalcet on alternate days could be an option for treatment of secondary HPT.Materials and methodsA retrospective clinical study was conducted on chronic maintenance hemodialysis patients. Patients with secondary HPT who received cinacalcet at a starting dose of 25 mg on alternate days were reviewed (low-dose group). Patients who were being treated with a standard dose of cinacalcet in the same period of time were selected as the control group. The primary outcome was difference in the percentage of patients achieving >30% reduction of intact parathyroid hormone (iPTH) levels at 16 weeks. The changes of serum iPTH and other biochemical data were also tested.ResultsA total of 30 patients (16 low doses and 14 controls) took part in the study. Baseline iPTH levels in the low-dose and control group were 1,065.9±477.7 and 1,214.1±497.6 pg/mL, respectively (p=0.413). The analysis showed that the percentage of patients who achieved the primary outcome showed little or no difference (33.3% in the low-dose group compared with 38.5% in the control group, p=1.0). Serum iPTH reduction during 16 weeks of study period in the low-dose and control group was 253.5±316.1 and 243.4±561.3 pg/mL, respectively (p=0.957). There was no difference in the adverse events between both groups.ConclusionAmong patients with secondary HPT, initial treatment with cinacalcet 25 mg on alternate days can decrease serum PTH levels. The role of low-dose cinacalcet in secondary HPT should be further determined in large-scale, randomized controlled trials.

Low-dose cholecalciferol supplementation and dual vitamin D therapy in haemodialysis patients

Traditionally, secondary hyperparathyroidism (SHPT) due to low calcitriol synthesis in failing kidneys has been treated with synthetic vitamin D receptor (VDR) activators. Recently, also the importance of low native vitamin D status beyond the issue of SHPT has been recognized in these patients. The aim of this work was to evaluate the effect of cholecalciferol supplementation in haemodialysis patients with low vitamin D serum levels. Another aim was to evaluate dual vitamin D therapy (cholecalciferol supplementation plus paricalcitol) in haemodialysis patients with vitamin D deficiency and concomitant SHPT. Ninety clinically stable maintenance haemodialysis patients were included. Supervised cholecalciferol supplementation was administered due to low vitamin D status. Patients with SHPT were also treated with synthetic VDR activator. Two pre hoc subgroups for statistical analysis were formed: patients treated solely with cholecalciferol (N=34; 5,000 IU once weekly) and patients treated with a combination of cholecalciferol (identical dose, i.e. 5,000 IU/week) plus paricalcitol (N=34, median dose 10 μg/week). Follow-up visit was scheduled 15 weeks later. Serum concentrations of calcidiol (25-D), parathyroid hormone (PTH) and beta-cross laps (CTX) were assessed at baseline and at follow-up. Serum calcium, phosphate and alkaline phosphatase (ALP) were monitored monthly. Only non-calcium gastrointestinal phosphate binders were administered. Dialysate calcium was 1.5 mmol/L in all patients, and no oral calcium-containing preparations were prescribed. Depending on data distribution, parametric or nonparametric statistical methods were used for comparison within each group (i.e. baseline vs. follow-up data) as well as between groups. In the whole group of 90 patients, mean baseline 25-D serum level was 20.3 (standard deviation 8.7) nmol/L, and it increased to 66.8 (19) nmol/L (p<0.0001) after supplementation. In both preformed subgroups, the effect of vitamin D supplementation was almost identical. In cholecalciferol monotherapy, 25-D levels increased from 18.4 (8.2) to 68.6 (21.2) and in dual vitamin D therapy from 18.4 (5.0) to 67.6 (17.7) nmol/L (both p<0.0001). In addition, both treatment modalities decreased serum PTH levels importantly: from 21.7 (interquartile range 17.3; 35.4) to 18.1 pmol/L (15.3; 24.7) in monotherapy (p=0.05) and from 38.6 (31.8; 53.3) to 33.9 pmol/L (26.1; 47.5) in dual vitamin D therapy (p=0.01). Serum calcium, phosphate, ALP and CTX did not change. We have not observed any episode of hypercalcemia in any subject during the whole period of follow-up. At baseline, slightly lower 25-D levels were observed in diabetic than in non-diabetic patients. This difference disappeared after substitution. Vitamin D status and its changes were not related to the patient's age. Low 25-D levels were very common in haemodialysis patients. They were safely and effectively corrected with supervised low-dose cholecalciferol supplementation. In patients with higher baseline PTH levels, dual vitamin D therapy (cholecalciferol plus paricalcitol) was safely and effectively used.

Paricalcitol for secondary hyperparathyroidism in renal transplantation.

Secondary hyperparathyroidism contributes to post-transplant CKD mineral and bone disorder. Paricalcitol, a selective vitamin D receptor activator, decreased serum parathyroid hormone levels and proteinuria in patients with secondary hyperparathyroidism. This single-center, prospective, randomized, crossover, open-label study compared the effect of 6-month treatment with paricalcitol (1 μg/d for 3 months and then uptitrated to 2 µg/d if tolerated) or nonparicalcitol therapy on serum parathyroid hormone levels (primary outcome), mineral metabolism, and proteinuria in 43 consenting recipients of renal transplants with secondary hyperparathyroidism. Participants were randomized 1:1 according to a computer-generated sequence. Compared with baseline, median (interquartile range) serum parathyroid hormone levels significantly declined on paricalcitol from 115.6 (94.8-152.0) to 63.3 (52.0-79.7) pg/ml (P<0.001) but not on nonparicalcitol therapy. At 6 months, levels significantly differed between treatments (P<0.001 by analysis of covariance). Serum bone-specific alkaline phosphatase and osteocalcin decreased on paricalcitol therapy only and significantly differed between treatments at 6 months (P<0.001 for all comparisons). At 6 months, urinary deoxypyridinoline-to-creatinine ratio and 24-hour proteinuria level decreased only on paricalcitol (P<0.05). L3 and L4 vertebral mineral bone density, assessed by dual-energy x-ray absorption, significantly improved with paricalcitol at 6 months (P<0.05 for both densities). Paricalcitol was well tolerated. Overall, 6-month paricalcitol supplementation reduced parathyroid hormone levels and proteinuria, attenuated bone remodeling and mineral loss, and reduced eGFR in renal transplant recipients with secondary hyperparathyroidism. Long-term studies are needed to monitor directly measured GFR, ensure that the bone remodeling and mineral effects are sustained, and determine if the reduction in proteinuria improves renal and cardiovascular outcomes.

The Short-Term Effects of Vitamin D Repletion on Cholesterol

Vitamin D deficiency is common and associated with dyslipidemia. However, it is unclear whether oral vitamin D supplementation improves the lipid profile. Therefore, we conducted a randomized, placebo-controlled trial to determine the short-term effects of vitamin D repletion on the lipid profile. One hundred fifty-one vitamin D-deficient (25-hydroxyvitamin D <20 ng/mL) adults with elevated risk for cardiovascular disease were randomized to receive either 50 000 IU of vitamin D3 weekly for 8 weeks or placebo. The primary outcome was the change in small low-density lipoprotein (LDL) particle number. Secondary outcomes included changes in other nuclear magnetic resonance-based and chemical lipid fractions. Vitamin D failed to improve the lipid profile. Compared with the placebo, vitamin D repletion did not change small LDL particle number (mean change, +18 nmol/L; 95% CI [-80 to +116 nmol/L]; P=0.63). There were also no changes in the chemical lipid profile: total cholesterol (+5.8 mg/dL, 95% CI [-1.4 to +13.0 mg/dL], P=0.14); LDL cholesterol (+3.8 mg/dL, 95% CI [-2.5 to +10.2 mg/dL], P=0.13); high-density lipoprotein cholesterol (+0.4 mg/dL 95% CI [-1.6 to +2.6 mg/dL], P=0.71); and triglycerides (+7.9 mg/dL 95% CI [-6.5 to +22.3 mg/dL]). In the vitamin D repletion group, exploratory multivariate regression analysis demonstrates that changes in LDL cholesterol were positively correlated with the changes in serum calcium (P<0.001) and inversely with the changes in serum parathyroid hormone (P=0.02). In contrast to the association between low 25-hydroxyvitamin D levels and dyslipidemia, correcting vitamin D deficiency in the short-term does not improve the lipid profile. Repletion of 25-hydroxyvitamin D levels raised serum calcium levels and decreased serum parathyroid hormone levels. These expected physiological responses to vitamin D therapy were correlated with a significant increase in LDL cholesterol. Clinical Trial Registration- URL: http://www.clinicaltrials.gov. Unique identifier: NCT01008384.

Effect of Alfacalcidol on Anemia in Renal Failure Patients

Background: Anemia is a major feature of chronic kidney disease (CKD). Additionally, secondary hyperparathyroidism (SHPT) has been associated with anemia in uremic patients. Administration of active vitamin D metabolites like alfacalcidol is established for PTH suppression and may also play a role in hematopoiesis. Aim:To investigate the effect of alfacalcidol on anemia and SHPT with end stage renal failure patients underwent hemodialysis. Subjects and Methods: In the present study 17 anemic patients over 15years, with serum level of PTH greater than 500pg/ml. The study was carried out by means of data collection and analysis of serum parathyroid hormone (PTH) and hemoglobin (Hb) levels in these patients. Results: Low serum PTH levels were detected in uremic patients treated with alfacalcidol. Also, in these patients, Hb levels increased. Serum PTH and Hb levels were inversely correlated. Conclusions: High-dose alfacalcidol can decrease serum PTH levels and elevate Hb level in uremic patients showing considerable resistance to Epoetin.

Parathyroid cell resistance to fibroblast growth factor 23 in secondary hyperparathyroidism of chronic kidney disease

Although fibroblast growth factor 23 (FGF23) acting through its receptor Klotho-FGFR1c decreases parathyroid hormone expression, this hormone is increased in chronic kidney disease despite an elevated serum FGF23. We measured possible factors that might contribute to the resistance of parathyroid glands to FGF23 in rats with the dietary adenine-induced model of chronic kidney disease. Quantitative immunohistochemical and reverse transcription-PCR analysis using laser capture microscopy showed that both Klotho and FGFR1 protein and mRNA levels were decreased in histological sections of the parathyroid glands. Recombinant FGF23 failed to decrease serum parathyroid hormone levels or activate the mitogen-activated protein kinase signaling pathway in the glands of rats with advanced experimental chronic kidney disease. In parathyroid gland organ culture, the addition of FGF23 decreased parathyroid hormone secretion and mRNA levels in control animals or rats with early but not advanced chronic kidney disease. Our results show that because of a downregulation of the Klotho-FGFR1c receptor complex, an increase of circulating FGF23 does not decrease parathyroid hormone levels in established chronic kidney disease. This in vivo resistance is sustained in parathyroid organ culture in vitro.

Sodium thiosulfate, bisphosphonates, and cinacalcet for treatment of calciphylaxis

The use of sodium thiosulfate, bisphosphonates, and cinacalcet for the treatment of calciphylaxis in adults with chronic kidney disease (CKD) is discussed. Calciphylaxis, generally characterized by extraosseous calcification of soft tissues, typically occurs in patients with stage 4 or 5 CKD. Very little data are available regarding the treatment of calciphylaxis. The role of elevated calcium and phosphate concentrations and hyperparathyroidism as risk factors for calciphylaxis has led clinicians to explore therapies that modify these factors, including sodium thiosulfate, bisphosphonates, and cinacalcet. Sodium thiosulfate has been shown to produce clinical improvement of calciphylaxis lesions. Bisphosphonates have been shown to be effective in animal models of calciphylaxis, and the mechanism of action is believed to be due to inhibition of macrophages and local proinflammatory cytokines and binding to calcified vascular smooth muscle cells to inhibit further arterial calcification. Cinacalcet, a calcimimetic agent that increases the sensitivity of the calcium-sensing receptor on the parathyroid gland to calcium, is believed to decrease serum parathyroid hormone levels and stabilize calcium and phosphate concentrations. Cinacalcet has been associated with improved pain control and ulcer healing. Cases describing the use of combination therapy with cinacalcet and sodium thiosulfate for the treatment of calciphylaxis have been published, but the positive effect on wound healing is difficult to attribute to a single drug. Evidence for the treatment of calciphylaxis with pharmacotherapeutic interventions is limited to case reports. Further research is necessary to fully describe the optimal use of sodium thiosulfate, bisphosphonates, and cinacalcet for the treatment of calciphylaxis, including their pharmacokinetics in adults with CKD, optimal dosing strategies, and duration of therapy.

22-Oxacalcitriol suppresses secondary hyperparathyroidism without inducing low bone turnover in dogs with renal failure

Calcitriol therapy suppresses serum levels of parathyroid hormone (PTH) in patients with renal failure but has several drawbacks, including hypercalcemia and/or marked suppression of bone turnover, which may lead to adynamic bone disease. A new vitamin D analogue, 22-oxacalcitriol (OCT), has been shown to have promising characteristics. This study was undertaken to determine the effects of OCT on serum PTH levels and bone turnover in states of normal or impaired renal function. Sixty dogs were either nephrectomized (Nx, N = 38) or sham-operated (Sham, N = 22). The animals received supplemental phosphate to enhance PTH secretion. Fourteen weeks after the start of phosphate supplementation, half of the Nx and Sham dogs received doses of OCT (three times per week); the other half were given vehicle for 60 weeks. Thereafter, the treatment modalities for a subset of animals were crossed over for an additional eight months. Biochemical and hormonal indices of calcium and bone metabolism were measured throughout the study, and bone biopsies were done at baseline, 60 weeks after OCT or vehicle treatment, and at the end of the crossover period. In Nx dogs, OCT significantly decreased serum PTH levels soon after the induction of renal insufficiency. In long-standing secondary hyperparathyroidism, OCT (0.03 microg/kg) stabilized serum PTH levels during the first months. Serum PTH levels rose thereafter, but the rise was less pronounced compared with baseline than the rise seen in Nx control. These effects were accompanied by episodes of hypercalcemia and hyperphosphatemia. In animals with normal renal function, OCT induced a transient decrease in serum PTH levels at a dose of 0.1 microg/kg, which was not sustained with lowering of the doses. In Nx dogs, OCT reversed abnormal bone formation, such as woven osteoid and fibrosis, but did not significantly alter the level of bone turnover. In addition, OCT improved mineralization lag time, (that is, the rate at which osteoid mineralizes) in both Nx and Sham dogs. These results indicate that even though OCT does not completely prevent the occurrence of hypercalcemia in experimental dogs with renal insufficiency, it may be of use in the management of secondary hyperparathyroidism because it does not induce low bone turnover and, therefore, does not increase the risk of adynamic bone disease.

Targeted inactivation of Npt2 in mice leads to severe renal phosphate wasting, hypercalciuria, and skeletal abnormalities.

Npt2 encodes a renal-specific, brush-border membrane Na+-phosphate (Pi) cotransporter that is expressed in the proximal tubule where the bulk of filtered Pi is reabsorbed. Mice deficient in the Npt2 gene were generated by targeted mutagenesis to define the role of Npt2 in the overall maintenance of Pi homeostasis, determine its impact on skeletal development, and clarify its relationship to autosomal disorders of renal Pi reabsorption in humans. Homozygous mutants (Npt2(-/-)) exhibit increased urinary Pi excretion, hypophosphatemia, an appropriate elevation in the serum concentration of 1,25-dihydroxyvitamin D with attendant hypercalcemia, hypercalciuria and decreased serum parathyroid hormone levels, and increased serum alkaline phosphatase activity. These biochemical features are typical of patients with hereditary hypophosphatemic rickets with hypercalciuria (HHRH), a Mendelian disorder of renal Pi reabsorption. However, unlike HHRH patients, Npt2(-/-) mice do not have rickets or osteomalacia. At weaning, Npt2(-/-) mice have poorly developed trabecular bone and retarded secondary ossification, but, with increasing age, there is a dramatic reversal and eventual overcompensation of the skeletal phenotype. Our findings demonstrate that Npt2 is a major regulator of Pi homeostasis and necessary for normal skeletal development.

Evidence for Both Abnormal Set Point of PTH Stimulation by Calcium and Adaptation to Serum Calcium in Hemodialysis Patients with Hyperparathyroidism

In vitro studies of parathyroid glands removed from dialysis patients with secondary hyperparathyroidism and hypercalcemia have demonstrated the presence of an increased set point of parathyroid hormone (PTH) stimulation by calcium (set point [PTHstim]), suggesting an intrinsic abnormality of the hyperplastic parathyroid cell. However, clinical studies on dialysis patients have not observed a correlation between the set point (PTHstim) and the magnitude of hyperparathyroidism. In the present study, 58 hemodialysis patients with moderate to severe hyperparathyroidism (mean PTH 780 +/- 377 pg/ml) were evaluated both before and after calcitriol treatment to establish the relationship among PTH, serum calcium, and the set point (PTHstim) and to determine whether changes in the serum calcium, as induced by calcitriol treatment, modified these relationships. Calcitriol treatment decreased serum PTH levels and increased the serum calcium and the setpoint (PTHstim); however, the increase in serum calcium was greater than the increase in the setpoint (PTHstim). Before treatment with calcitriol, the correlation between the set point (PTHstim) and the serum calcium was r = 0.82, p < 0.001, and between the set point (PTHstim) and PTH was r = 0.39, p = 0.002. After treatment with calcitriol, the correlation between the set point (PTHstim) and the serum calcium remained significant (r = 0.70, p < 0.001), but the correlation between the set point (PTHstim) and PTH was no longer significant (r = 0.09); moreover, a significant correlation was present between the change in the set point (PTHstim) and the change in serum calcium that resulted from calcitriol treatment (r = 0.73, p < 0.001). The correlation between the residual values (deviation from the regression line) of the set point (PTHstim), derived from the correlation between PTH and the set point (PTHstim), and serum calcium was r = 0.77, p < 0.001 before calcitriol and r = 0.72, p < 0.001 after calcitriol. In conclusion, the set point (PTHstim) increased after a sustained increase in the serum calcium, suggesting an adaptation of the set point to the existing serum calcium; the increase in serum calcium resulting from calcitriol treatment was greater than the increase in the set point (PTHstim); the set point (PTHstim) was greater in hemodialysis patients with higher serum PTH levels; and the correlation between PTH and the set point (PTHstim) may be obscured because the serum calcium directly modifies the set point (PTHstim).

The Renal Bone Diseases in Children Treated With Dialysis

Renal osteodystrophy represents a spectrum from high- to low-turnover bone lesions. The specific pattern, however, may change during selected therapeutic interventions. As in the past, osteitis fibrosa remains the most frequent histologic lesion in pediatric patients on dialysis, although recently the prevalence of low-turnover bone lesions without aluminum toxicity has been increasing in the pediatric population. This may be a consequence of aggressive calcitriol and calcium therapy. The different factors involved in the development of secondary hyperparathyroidism include hyperphosphatemia, hypocalcemia, altered vitamin D synthesis, impairments in parathyroid hormone (PTH) secretion and metabolism, and, recently, possible downregulation of renal PTH/PTH-rP messenger RNA receptor. New developments in molecular biology have demonstrated the relationship between vitamin D and PTH. The use of high-dose pulse intravenous, intraperitoneal, and oral calcitriol therapy has significantly decreased serum PTH levels and retarded the progression of osteitis fibrosa. These therapeutic interventions, however, may have led to the development of adynamic bone lesions. The impact of adynamic bone lesions in the young and growing skeleton remains to be determined.

Effects of 7-isopropoxy-3-phenyl-4H-1-benzopyran-4-one (ipriflavone) on serum levels of calcitonin and parathyroid hormone in patients with adult-onset diabetes

The effects of 1α-hydroxycholecalciferol [1α(OH)D3] and 7-isopropoxy-3-phenyl-4H-1-benzopyran-4-one [ipriflavone (IP)] on the serum concentrations of parathyroid hormone (PTH) and calcitonin (CTN) were studied in patients with adult-onset diabetes (NIDDM). A group of 122 NIDDM patients with unrestricted caloric intake were divided by random sampling into dietary (D) and non-dietary (ND) groups. Group D was placed on a calorie-restricted diet while group ND remained free of dietary restrictions. Two years after the groups were so divided, the groups were further divided by random sampling into 2 sub-groups (D1 and D2; ND1 and ND2). Groups D1 and ND1 received 1α(OH)D3 for 2 months, followed by combined IP/1α(OH)D3 administration for 6 months, and groups D2 and ND2 received a placebo in place of 1α(OH)D3. Serum PTH levels were higher and serum CTN levels were lower in group D than in group ND. Administration of 1α(OH)D3 to group D1 patients decreased serum PTH levels and increased serum calcium concentration, although serum CTN levels were not affected. Serum CTN levels were found to increase significantly (p<0.01), without changes in serum PTH concentrations, during the 6 months, combination treatment of 1α(OH)D3 and IP. IP also increased CTN levels in group ND2 and in patients in group D2 who had no prior 1α(OH)D3 treatment. IP did not, however, increase serum CTN levels significantly in patients whose serum PTH concentration was relatively high (500 pg/ml or more). These results suggest that IP is suitable for increasing serum CTN levels in NIDDM patients, and that its action is dependent on serum PTH levels.

Calcium and Salmon Calcitonin in Treatment of Osteoporosis*

Calcitonin has been considered of therapeutic value in osteoporosis because of its effects in tissue culture. In the whole animal, however, the predominant result seems to be hypocalcemia, which might be expected to have the opposite effect of stimulating parathyroid hormone secretion and therefore resorption of bone. Indeed, in a short term study of 3- and 4-month duration in osteoporotic women, this was found to be so. A combination of calcium and calcitonin was therefore considered a more promising therapeutic alternative for this disease. Calcium was given to 26 patients, alone or with vitamin D, for a period of 15 months, and the effects on serum and urine calcium and phosphorus and on bone resorption and formation were evaluated. Calcium and vitamin D decreased serum parathyroid hormone levels, reduced bone resorption, and increased urinary calcium. The addition of calcitonin to the calcium and vitamin D did not seem to change these effects. Neither form of treatment resulted in change of bone mass. Calcium, with or without vitamin D supplements, may prevent the development of osteoporosis, but it seems unlikely that calcitonin has any additional desirable effect in the disease.